PMC:29006 / 9073-13491
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/29006","sourcedb":"PMC","sourceid":"29006","source_url":"http://www.ncbi.nlm.nih.gov/pmc/29006","text":"Discussion\nPPHN is a common endpoint of several very different pathophysiological \t\t mechanisms. It is extremely important to understand the underlying etiology of \t\t PPHN, as therapeutic interventions must be tailored to specific circumstances; \t\t for example, PPHN associated with hyaline membrane disease should first be \t\t treated with surfactant therapy.\nMaintenance of adequate circulating blood volume, systemic vascular \t\t resistance, and optimal lung inflation are essential for the management of \t\t PPHN. High-frequency ventilation has been introduced as a mode of therapy in \t\t PPHN. There were no randomized studies of HFOV in the management of infants \t\t with PPHN, but attention has been focused on the potential of HFOV to reduce \t\t the need for extracorporeal membrane oxygenation (ECMO). A number of reports \t\t identify a number of infants who, although referred for ECMO, survived without \t\t using this type of intervention [6,7].\nA comparison between HFOV and INO in reducing the need for ECMO has \t\t been studied. Kinsella et al [8] combined HFOV \t\t and INO in the treatment of infants with hypoxic respiratory failure and PPHN \t\t who were ECMO candidates. These authors found no difference in the need for \t\t ECMO or death in the INO group compared with the HFOV group, and they suggest \t\t that combined treatment with INO and HFOV may improve outcome.\nIn this study, we found that 75% of infants with PPHN who failed HFOV \t\t responded to INO therapy and 62.5% survived to discharge. Recently, the NINOS \t\t Study Group has conducted a study to evaluate whether INO would reduce the \t\t incidence of death or the need for ECMO in infants with hypoxic respiratory \t\t failure [9]. HFOV was used in 55% of the infants. The \t\t authors found that treatment with INO resulted in a significant reduction in \t\t the combined incidence of death in less than 120 days or the need for ECMO. \t\t Moreover, Roberts et al [10] studied 58 \t\t full-term infants with severe hypoxemia and PPHN who were randomized to receive \t\t either INO or nitrogen. They found that INO improved systemic oxygenation in \t\t these infants and they suggest that INO may reduce the need for more invasive \t\t treatment.\nIn this study, we found that 61.1% of the responders responded within \t\t the first 2h after the initiation of INO and their response sustained to the \t\t end of the treatment and the remaining neonates showed a gradual response \t\t throughout the course of INO. Similarly Goldman et al [11] evaluated INO in a group of 25 severely hypoxic term \t\t neonates and identified four patterns of response. Two neonates did not \t\t respond, nine neonates who responded well initially then failed within 24 h, 11 \t\t neonates responded and sustained that response, and three neonates responded to \t\t INO but required high doses for prolonged periods of time. We also found that \t\t 25% failed INO therapy, most likely as a result of severe pulmonary hypoplasia \t\t seen in CDH, and severe lung damage due to severe hypoxia as in asphyxia and \t\t RDS. A number of studies have noted a general lack of a sustained improvement \t\t in oxygenation in response to INO in the management of CDH [12,13,14]. In \t\t this study ECMO was not used as an alternative therapy for the INO \t\t non-responders because it was not available in our hospital for neonates.\nIt has been observed that some infants who showed a dramatic response \t\t to INO developed a decrease in oxygenation when INO was discontinued. This \t\t response may reflect downregulation of endogenous nitric oxide synthase \t\t activity secondary to the administration of exogenous nitric oxide [15]. In addition INO may increase the concentration of \t\t phosphodiesterase, which then degrades cyclic GMP when INO is discontinued, \t\t resulting in vaso-constriction. In this study, four infants became \t\t INO-dependent and successfully weaned from INO following the use of \t\t phosphodiesterase inhibitor (dipyridamole) [16]. Study \t\t of the mechanism of INO dependency may give insight into new therapies that \t\t augment the pulmonary vasodilatory effect of INO and the activity of the \t\t endogenous NO system.\nIn conclusion, the administration of INO at 20ppm, following adequate \t\t ventilation for a maximum of 2h without significant response could be used to \t\t identify the majority of the non-responders. In these situations, other means \t\t of therapy, such as ECMO, could be considered.","divisions":[{"label":"Title","span":{"begin":0,"end":10}}],"tracks":[{"project":"2_test","denotations":[{"id":"11056716-9032045-23487244","span":{"begin":1926,"end":1928},"obj":"9032045"},{"id":"11056716-8885950-23487245","span":{"begin":2484,"end":2486},"obj":"8885950"}],"attributes":[{"subj":"11056716-9032045-23487244","pred":"source","obj":"2_test"},{"subj":"11056716-8885950-23487245","pred":"source","obj":"2_test"}]},{"project":"Colil","denotations":[{"id":"T1","span":{"begin":2484,"end":2486},"obj":"8885950"},{"id":"T2","span":{"begin":1926,"end":1928},"obj":"9032045"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/"}],"attributes":[{"subj":"T1","pred":"source","obj":"Colil"},{"subj":"T2","pred":"source","obj":"Colil"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#dd93ec","default":true},{"id":"Colil","color":"#93ecc3"}]}]}}